Drugs List

Therapeutic Indications

Uses

Treatment of relapsing-remitting multiple sclerosis

Contraindications

Absolute lymphocyte count below 0.5 x 10 to the power of 9/L
Children under 18 years
Severe infection
Breastfeeding
Pregnancy
Progressive multifocal leukoencephalopathy (PML)

Precautions and Warnings

Antibodies to JC virus
Lymphopenia
Moderate renal impairment
Severe gastrointestinal disorder
Severe hepatic impairment

Treatment to be initiated and supervised by a specialist
Capsules should not be opened or crushed
A recent (within 3 months) MRI should be available prior to treatment
Monitor renal and hepatic function before and during treatment
Perform full blood count before treatment
Monitor full blood counts every 3 months
Advise patient that flushing reactions may occur
Advise patient to report symptoms of infection immediately
Advise patient to seek medical advice if severe flushing occurs
Consider stopping if lymphocytes below 0.5x10 to power 9/L for 6 months
Discontinue if anaphylactoid reaction occurs
Discontinue if Progressive multifocal leukoencephalopathy (PML) develops
Discontinue treatment if patient develops a serious infection
Evaluate risk if lymphocyte count below 0.8x10 to power9/L for 6 months
Female: Ensure adequate contraception during treatment
Advise patient to report symptoms of herpes zoster urgently

Prior to initiating treatment with diroximel fumarate, renal function (e.g. creatinine, blood urea nitrogen and urinalysis) should be assessed prior to treatment, after 3 and 6 months of treatment and 6 to 12 monthly thereafter as clinically indicated. Serum aminotransferases (e.g. alanine aminotransferase (ALT), aspartate aminotransferase (AST)) and total bilirubin levels are recommended to be assessed before treatment is initiated and during treatment as clinically indicated. Regular monitoring of absolute lymphocyte counts is recommended in lymphopenia patients with lymphocyte count below the normal limit due to an increased risk of Progressive Multifocal Leukoencephalopathy (PML). Magnetic resonance image (MRI) should be performed immediately in case of clinical suspicion of PML. Withhold treatment and perform John Cunningham Virus (JCV) DNA in cerobrospinal fluid (CSF) by quantitative polymerase chain reaction (PCR) methodology at the first sign or symptom suggestive of PML. Consider a short course of acetylsalicylic acid 75mg in patients who experience intolerable flushing.

Cases of herpes zoster may occur at any time during the treatment. Monitor signs and symptoms of herpes zoster in particular when lymphocytopenia occurs simultaneously. Treat appropriately and withhold the treatment of diroximel fumarate in case of severe infections. Resume treatment only after the infections have been resolved.

Always consider fanconi syndrome and perform appropriate examinations in case of unclear symptoms. Discontinuation of diroximel fumarate treatment in the early diagnosis of fanconi syndrome can prevent the onset of renal impairment and osteomalacia.

Pregnancy and Lactation

Pregnancy

Diroximel fumarate is contraindicated during pregnancy.
The manufacturer does not recommend using diroximel fumarate during pregnancy. The manufacturer advises that diroximel fumarate should only be used during pregnancy if the potential benefits outweigh the risk to the foetus. Animal studies have shown reproductive toxicity. Human data is limited and as such a potential risk cannot be ruled out.

Lactation

Diroximel fumarate is contraindicated during breastfeeding.
The manufacturer advises that the patient either discontinues diroximel fumarate treatment or discontinues breastfeeding. The presence of diroximel fumarate in human breast milk and the effects on exposed infants are unknown.

Side Effects

Abdominal pain
Alanine aminotransferase increased
Albuminuria
Anaphylaxis
Angioedema
Aspartate aminotransferase increased
Burning sensation
Diarrhoea
Drug-induced liver injury
Dyspepsia
Dyspnoea
Erythema
Feeling hot
Flushing
Gastritis
Gastro-enteritis
Gastrointestinal disorder
Herpes zoster
Hot flushes
Hypersensitivity reactions
Hypotension
Hypoxia
Ketonuria
Leukopenia
Lymphopenia
Nausea
Progressive multifocal leukoencephalopathy (PML)
Proteinuria
Pruritus
Rash
Rhinorrhoea
Thrombocytopenia
Upper abdominal pain
Urticaria
Vomiting
White blood cell count decreased

Presentation

Oral formulation of diroximel fumarate.

Drugs List

Therapeutic Indications

Uses

Treatment of relapsing-remitting multiple sclerosis

Dosage

Start treatment gradually to minimise the occurrence of flushing and gastrointestinal adverse reactions.

Adults

Additional Dosage Information

Contraindications

Absolute lymphocyte count below 0.5 x 10 to the power of 9/L
Children under 18 years
Severe infection
Breastfeeding
Pregnancy
Progressive multifocal leukoencephalopathy (PML)

Precautions and Warnings

Antibodies to JC virus
Lymphopenia
Moderate renal impairment
Severe gastrointestinal disorder
Severe hepatic impairment

Treatment to be initiated and supervised by a specialist
Capsules should not be opened or crushed
A recent (within 3 months) MRI should be available prior to treatment
Monitor renal and hepatic function before and during treatment
Perform full blood count before treatment
Monitor full blood counts every 3 months
Advise patient that flushing reactions may occur
Advise patient to report symptoms of infection immediately
Advise patient to seek medical advice if severe flushing occurs
Consider stopping if lymphocytes below 0.5x10 to power 9/L for 6 months
Discontinue if anaphylactoid reaction occurs
Discontinue if Progressive multifocal leukoencephalopathy (PML) develops
Discontinue treatment if patient develops a serious infection
Evaluate risk if lymphocyte count below 0.8x10 to power9/L for 6 months
Female: Ensure adequate contraception during treatment
Advise patient to report symptoms of herpes zoster urgently

Prior to initiating treatment with diroximel fumarate, renal function (e.g. creatinine, blood urea nitrogen and urinalysis) should be assessed prior to treatment, after 3 and 6 months of treatment and 6 to 12 monthly thereafter as clinically indicated. Serum aminotransferases (e.g. alanine aminotransferase (ALT), aspartate aminotransferase (AST)) and total bilirubin levels are recommended to be assessed before treatment is initiated and during treatment as clinically indicated. Regular monitoring of absolute lymphocyte counts is recommended in lymphopenia patients with lymphocyte count below the normal limit due to an increased risk of Progressive Multifocal Leukoencephalopathy (PML). Magnetic resonance image (MRI) should be performed immediately in case of clinical suspicion of PML. Withhold treatment and perform John Cunningham Virus (JCV) DNA in cerobrospinal fluid (CSF) by quantitative polymerase chain reaction (PCR) methodology at the first sign or symptom suggestive of PML. Consider a short course of acetylsalicylic acid 75mg in patients who experience intolerable flushing.

Cases of herpes zoster may occur at any time during the treatment. Monitor signs and symptoms of herpes zoster in particular when lymphocytopenia occurs simultaneously. Treat appropriately and withhold the treatment of diroximel fumarate in case of severe infections. Resume treatment only after the infections have been resolved.

Always consider fanconi syndrome and perform appropriate examinations in case of unclear symptoms. Discontinuation of diroximel fumarate treatment in the early diagnosis of fanconi syndrome can prevent the onset of renal impairment and osteomalacia.

Pregnancy and Lactation

Pregnancy

Diroximel fumarate is contraindicated during pregnancy.
The manufacturer does not recommend using diroximel fumarate during pregnancy. The manufacturer advises that diroximel fumarate should only be used during pregnancy if the potential benefits outweigh the risk to the foetus. Animal studies have shown reproductive toxicity. Human data is limited and as such a potential risk cannot be ruled out.

Lactation

Diroximel fumarate is contraindicated during breastfeeding.
The manufacturer advises that the patient either discontinues diroximel fumarate treatment or discontinues breastfeeding. The presence of diroximel fumarate in human breast milk and the effects on exposed infants are unknown.

Side Effects

Abdominal pain
Alanine aminotransferase increased
Albuminuria
Anaphylaxis
Angioedema
Aspartate aminotransferase increased
Burning sensation
Diarrhoea
Drug-induced liver injury
Dyspepsia
Dyspnoea
Erythema
Feeling hot
Flushing
Gastritis
Gastro-enteritis
Gastrointestinal disorder
Herpes zoster
Hot flushes
Hypersensitivity reactions
Hypotension
Hypoxia
Ketonuria
Leukopenia
Lymphopenia
Nausea
Progressive multifocal leukoencephalopathy (PML)
Proteinuria
Pruritus
Rash
Rhinorrhoea
Thrombocytopenia
Upper abdominal pain
Urticaria
Vomiting
White blood cell count decreased

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Reference Sources

Summary of Product Characteristics: Vumerity 231mg gastro-resistant hard capsules. Biogen Idec Ltd. Revised November 2021.